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Gastric cancer and micrometastases: first updating

Romeo Giuli MD, resident.
School of General and Emergency Surgery.
University of Siena.   Italy.

July 2001.     Review Article.

To previous article about micrometastases
To the second updating
To the third updating
To the fourth updating

Fukagawa et al underline that there is a debate regarding the terminology of micrometastases.
Their definition of micrometastases is the presence of tumour cells in regional lymph nodes not detected on routine H&E staining. Many lymph node metastases measure <2 mm in greatest dimension. Moreover they arbitrarily divide the metastases into single cells and cluster types. They find no differences in outcome between the two types .

There is a debate regarding whether the identification of isolated tumor cells is of clinical significance and whether it should be incorporated into staging systems ( 1 ).
Hermanek et al stress that the inclusion of isolated tumour cells ( ITC ) into the current staging system has been discussed, because they may be used as selection criteria for more aggressive treatment, as well as surrogate markers to monitor the efficiency of adjuvant therapy.
However the indipendent prognostic significance of ITC remains to be proven. In fact if we include such findings in the TNM and R classifications stage migration can occur and can invalidate comparisons of treatment results ( 2 ).
Schenemann et al on the contrary affirm that if immunohistochemically identifiable cells in lymph nodes represent viable tumor cells, this information should be incorporated into the staging nomenclature of the International Union against Cancer ( 3 ).

Fukagawa et al studie 107 patients with pathologic T2N0M0 gastric carcinoma treated at the National cancer Center Hospital of Tokyo, between 1984-1990.
They conclude that occult micrometastases to regional lymph nodes are not associated with poorer survival in patients with pT2N0 gastric carcinoma who underwent extended lymph node dissection.
They had expected that there would be some association between the presence of micrometastases and recurrence of gastric carcinoma, but this was not the case.
The significant incidence of micrometastases means that this remains local disease, and the micrometastases are not a marker of systemic disease. This is in favour of the policy of performing comprehensive lymph node dissection. The relatively high incidence of micrometastases in lymph nodes of patients with pT2N0 disease and the excellent prognosis of patients after undergoing extended dissection confirm that surgery is quite appropriate if it is done with a very low operative mortality.

The 35.5% of the patients of this study have micrometastases, with approximately equal numbers of single cell type and cluster type metastases.
Micrometastases are more likely to be found in subserosal tumours, large tumours, and tumours with lymphatic or vascular invasion ( 1 ).


1) Fukagawa T, Mitsuru Sasako, Gregory Bruce Mann, Takeshi Sano, Hitoshi Katai, Keiichi Maruyama, Yukihiro Nakanishi, Tadakazu Shimoda. Immunohistochemical detected micrometastes of the lymph nodes in patients with gastric carcinoma. Cancer 2001; 92: 753-60.

2) Paul Hermanek, Robert VP Hutter, Leslie H Sobin, Christian Wittekind. Classification of isolated tumor cells and micrometastases. Cancer 1999; 86: 2668-73.

3) Schenemann P et al. Tumorigenic potential of apparently tumor free lymph nodes. N Engl J Med 1999; 340: 1687.

4) O' Sullivan GC et al. Micrometastases: marker of metastatic potential or evidence of residual disease. Gut 1997; 40: 512-5.

5) Kikuchi Y et al. Immunohistochemical detection of lymph node microinvolvement in node negative gastric cancer. Gastric Cancer 1999; 2: 173-8.

6) Cai J et al. Clinico-pathological value of immunohistochemical detection of occult involvement in pT3N0 gastric cancer. Gastric Cancer. 1999; 2: 95-100.

7) Natsugoe S et al. Paraaortic lymph node micrometastases and tumor cell microinvolvement in advanced gastric carcinoma. Gastric Cancer 1999; 2: 179-85.

8) Whiting JL et al. Redefining surgery for gastric cancer. Gastric Cancer 1999; 2: 226-9.

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